《Nature》造血干细胞的惊人发现

　　

生物通报道，哈佛医学院，HHMI研究所的科研人员在最新的Nature上发表脂肪细胞与造血研究的最新进展，Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment。

 

造血干细胞的微环境中包含大量的成骨细胞和内皮细胞，通常还含有少量的脂肪细胞。一般情况下，脂肪细胞在骨髓造血干细胞微环境中的含量是很低的，在临床上，如果检测发现骨髓中含有大量脂肪细胞，就表明骨髓发育不良，不利于生成造血细胞。比如，临床上的恶性贫血和白血病都伴随着脂肪浸润骨髓的临床症状。

 

一直以来，脂肪细胞的出现代表造血功能异常，关于脂肪细胞对造血功能的调节功能却没有报道。

 

George Q. Daley等人的研究结果是惊人的，脂肪细胞其实对造血作用具有关键的调节作用。用小鼠所做实验表明，脂肪细胞数量多的骨髓所含造血干细胞和祖细胞要少于脂肪细胞数量少的骨髓。遗传上不含脂肪细胞的小鼠和用一种阻断脂肪细胞产生的药物处理过的小鼠，在经过一次骨髓移植之后产生新的血细胞的速度要比野生型小鼠快，说明阻断骨髓脂肪细胞生成在临床骨髓移植中也许可帮助造血作用的恢复。

 

这些研究结果表明，脂肪细胞是调节造血功能的负调节因子。

（生物通 小茜）

生物通推荐原文摘要：

 

Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment

Olaia Naveiras1, Valentina Nardi1,4, Pamela L. Wenzel1,4, Peter V. Hauschka2, Frederic Fahey3 & George Q. Daley1

 

Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Division of Hematology, Brigham and Women's Hospital; Harvard Stem Cell Institute; Manton Center for Orphan Diseases; Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA

Departments of Orthopaedic Surgery and Oral and Developmental Biology, Harvard Medical School and School of Dental Medicine, Boston, Massachusetts, 02115, USA

Department of Radiology, Division of Nuclear Medicine/PET, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA

 

【Abstract】

Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow1, 2, 3. Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia4. To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes5, and in mice treated with the peroxisome proliferator-activated receptor- inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis6, marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.